Chemistry is an experimental science, Formula: C21H15F12NO, and the best way to enjoy it and learn about it is performing experiments.Introducing a new discovery about 848821-76-1, Name is (S)-Bis(3,5-bis(trifluoromethyl)phenyl)(pyrrolidin-2-yl)methanol
Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5
The human cytochrome P450 (CYP) enzymes CYP3A4 and CYP3A5 metabolize most drugs and have high similarities in their structure and substrate preference. Whereas CYP3A4 is predominantly expressed in the liver, CYP3A5 is upregulated in cancer, contributing to drug resistance. Selective inhibitors of CYP3A5 are, therefore, critical to validating it as a therapeutic target. Here we report clobetasol propionate (clobetasol) as a potent and selective CYP3A5 inhibitor identified by high-Throughput screening using enzymatic and cell-based assays. Molecular dynamics simulations suggest a close proximity of clobetasol to the heme in CYP3A5 but not in CYP3A4. UV-visible spectroscopy and electron paramagnetic resonance analyses confirmed the formation of an inhibitory type I heme-clobetasol complex in CYP3A5 but not in CYP3A4, thus explaining the CYP3A5 selectivity of clobetasol. Our results provide a structural basis for selective CYP3A5 inhibition, along with mechanistic insights, and highlight clobetasol as an important chemical tool for target validation.
Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Formula: C21H15F12NO, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 848821-76-1, in my other articles.
Reference：
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI